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Day and Night Closed-loop in Young People With Type 1 Diabetes (DAN05)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified March 2017 by Jaeb Center for Health Research
Sponsor:
Collaborators:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Cambridge University Hospitals NHS Foundation Trust
University of Colorado Denver School of Medicine Barbara Davis Center
International Diabetes Center at Park Nicollet
The Leeds Teaching Hospitals NHS Trust
Stanford University
Yale University
Information provided by (Responsible Party):
Jaeb Center for Health Research
ClinicalTrials.gov Identifier:
NCT02925299
First received: October 4, 2016
Last updated: March 1, 2017
Last verified: March 2017
  Purpose

The main study objective is to determine whether 24/7 automated closed-loop glucose control combined with low glucose feature will improve glucose control as measured by HbA1c.

This is an open-label, multi-centre, multi-national, single-period, randomised, parallel group design study, involving a 12 month period of home study during which day and night glucose levels will be controlled either by a closed-loop system combined with low glucose feature (intervention group) or by insulin pump therapy alone (control group).

It is expected that a total of up to 150 subjects (aiming for 130 randomised subjects) with type 1 diabetes will be recruited through paediatric outpatient diabetes clinics of the investigation centres. Participants will all be on subcutaneous insulin pump therapy.

Subjects in the intervention group will have proven competencies both in the use of the study insulin pump and the study continuous glucose monitoring (CGM) device, and will receive appropriate training in the safe use of closed-loop insulin delivery system and low glucose feature. All subjects will have regular contact with the study team during the home study phase including 24/7 telephone support. The primary outcome is between group differences in HbA1c levels at 12 months post study arm initiation. Secondary outcomes are the time spent in the glucose target (3.9 to 10.0mmol/l; 70 to 180mg/dl), time spent with glucose levels above and below target, as recorded by CGM, and other CGM-based metrics. Safety evaluation comprises assessment of the frequency of severe hypoglycaemic episodes and diabetic ketoacidosis (DKA).


Condition Intervention
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Endocrine System Diseases
Autoimmune Diseases
Device: FlorenceM
Device: Insulin pump therapy

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: An Open-label, Multi-centre, Randomized, Single-period, Parallel Study to Assess the Efficacy, Safety and Utility of 12 Month Day-and-night Automated Closed-loop Insulin Delivery Under Free Living Conditions Compared to Insulin Pump Therapy in Children and Adolescents With Type 1 Diabetes

Resource links provided by NLM:


Further study details as provided by Jaeb Center for Health Research:

Primary Outcome Measures:
  • The primary outcome is the centralised measurement of glycated haemoglobin (HbA1c) at 12 months. [ Time Frame: HbA1c will be taken at baseline, 3, 6, 9 and 12 months ]
    The objective is to assess efficacy of day and night automated closed-loop glucose control combined with low glucose feature in improving HbA1c, as compared with insulin pump therapy alone.


Secondary Outcome Measures:
  • Time spent in the target glucose range (3.9 to 10mmol/l) (70 to 180mg/dl) [ Time Frame: 12 months ]
    Secondary endpoints regarding glucose levels will be based on sensor glucose data.

  • Time spent below target glucose (3.9mmol/l)(70mg/dl) [ Time Frame: 12 months ]
    Secondary endpoints regarding glucose levels will be based on sensor glucose data.

  • Time spent above target glucose (10.0 mmol/l) (180 mg/dl) [ Time Frame: 12 months ]
    Secondary endpoints regarding glucose levels will be based on sensor glucose data.

  • Mean and standard deviation or percentiles sensor glucose [ Time Frame: 12 months ]
    Secondary endpoints regarding glucose levels will be based on sensor glucose data.

  • Coefficient of variation of glucose levels [ Time Frame: 12 months ]
    Secondary endpoints regarding glucose levels will be based on sensor glucose data.

  • Time with glucose levels < 3.5 mmol/l (63 mg/dl) [ Time Frame: 12 months ]
    Secondary endpoints regarding glucose levels will be based on sensor glucose data.

  • Time with glucose levels <2.8 mmol/l (50 mg/dl) [ Time Frame: 12 months ]
    Secondary endpoints regarding glucose levels will be based on sensor glucose data.

  • Time with glucose levels in significant hyperglycaemia (glucose levels > 16.7 mmol/l) (300mg/dl) [ Time Frame: 12 months ]
    Secondary endpoints regarding glucose levels will be based on sensor glucose data.

  • Changes in total basal and bolus insulin dose [ Time Frame: 12 months ]
    Secondary endpoints regarding glucose levels will be based on CRF and insulin pump data.

  • AUC of glucose below 3.5mmol/l (63mg/dl) [ Time Frame: 12 months ]
    Secondary endpoints regarding glucose levels will be based on sensor glucose data.


Other Outcome Measures:
  • Safety Evaluation [ Time Frame: 12 months ]
    Frequency of severe hypoglycaemic episodes as defined by American Diabetes Association (adolescents), and International Society for Pediatric and Adolescent Diabetes (children), frequency of diabetic ketoacidosis (DKA), frequency of severe hyperglycaemia (>16.7 mmol/l)(>300mg/dl) with significant ketosis (plasma ketones >0.6mmol/l) and nature and severity of other adverse events

  • Utility evaluation [ Time Frame: 12 months ]
    Assessment of the frequency and duration of use of the closed-loop system

  • Human Factors Assessment [ Time Frame: 12 months ]
    Cognitive, emotional, and behavioural characteristics of participating subjects and family members and their response to the closed-loop system and clinical trial will be assessed gathering both quantitative (validated surveys) and qualitative data (focus groups)

  • Health Economic Evaluation [ Time Frame: 12 months ]
    Cost utility analysis on the benefits of closed loop insulin delivery to inform reimbursement decision-making


Estimated Enrollment: 150
Anticipated Study Start Date: April 2017
Estimated Study Completion Date: October 2018
Estimated Primary Completion Date: October 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 24/7 closed loop insulin delivery
The study system includes (1) a CGM that measures glucose levels, (2) a computer program on a smartphone that determines how much insulin is needed, and (3) an insulin pump that delivers the insulin. The name of this closed-loop system is FlorenceM. Half of the individuals taking part in the study will use the study system for 12 months.
Device: FlorenceM

The automated closed loop system (FlorenceM) will consist of:

Next generation sensor augmented Medtronic insulin pump 640G (Medtronic Minimed, CA, USA) incorporating the Medtronic Enlite 3 CGM and glucose suspend feature.

An Android smartphone containing the Cambridge model predictive algorithm and communicating wirelessly with the insulin pump using a proprietary translator device.

Active Comparator: Insulin pump therapy
Half of the Subjects will continue using their own insulin pump for 12 months.
Device: Insulin pump therapy
Subjects will continue using their own insulin pump for 12 months.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   6 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥6 and <19 years
  2. Type 1 diabetes as defined by WHO (51) for at least 1 year [WHO definition: 'The aetiological type named type 1 encompasses the majority of cases with are primarily due to beta-cell destruction, and are prone to ketoacidosis. Type 1 includes those cases attributable to an autoimmune process, as well as those with beta-cell destruction for which neither an aetiology nor a pathogenesis is known (idiopathic). It does not include those forms of beta-cell destruction or failure to which specific causes can be assigned (e.g. cystic fibrosis, mitochondrial defects, etc.).']
  3. Use of an insulin pump for at least 3 months, with good knowledge of insulin self-adjustment by subject or caregiver as judged by the investigator
  4. Using U-100 rapid acting insulin analogues insulin Aspart or Lispro only
  5. Willing to perform regular finger-prick blood glucose monitoring, with at least 4 blood glucose measurements per day day
  6. Screening HbA1c ≥ 7.5% (58 mmol/mol) and ≤10 % (86mmol/mol) based on analysis from local laboratory
  7. Literate in English
  8. Willing to wear glucose sensor
  9. Willing to wear closed-loop system at home
  10. Willing to follow study specific instructions
  11. Willing to upload pump and CGM data at regular intervals
  12. Access to WiFi.
  13. Lives with someone who is trained to administer intramuscular glucagon and is able to seek emergency assistance

Exclusion Criteria:

  1. Living alone
  2. Use of real-time CGM on regular basis (use of any real-time CGM device longer than 1 month during preceding 3 months, i.e. >33% of time)
  3. Any other physical or psychological disease likely to interfere with the normal conduct of the study and interpretation of the study results as judged by the investigator
  4. Untreated coeliac disease, adrenal insufficiency, or untreated thyroid disease
  5. Current treatment with drugs known to interfere with glucose metabolism, e.g. systemic corticosteroids, non-selective beta-blockers and MAO inhibitors etc.
  6. Known or suspected allergy to insulin
  7. Clinically significant nephropathy (eGFR < 45ml/min) or on dialysis, neuropathy or active retinopathy (defined as presence of maculopathy or proliferative changes) as judged by the investigator
  8. Recurrent incidents of severe hypoglycaemia (>1 episode) during the previous 6 months (adolescents: severe hypoglycaemia is defined as an event requiring assistance of another person to actively administer carbohydrates, glucagon, or take other corrective actions including episodes of hypoglycaemia severe enough to cause unconsciousness, seizures or attendance at hospital; children: severe hypoglycaemia is defined as an event associated with a seizure or loss of consciousness)
  9. Recurrent incidents of diabetic ketoacidosis (>1 episode) during previous 6 months
  10. Unwilling to avoid regular use of acetaminophen
  11. Lack of reliable telephone facility for contact
  12. Total daily insulin dose ≥ 2 IU/kg/day
  13. Total daily insulin dose < 15 IU/day
  14. Pregnancy, planned pregnancy, or breast feeding
  15. Severe visual impairment
  16. Severe hearing impairment
  17. Seizure disorder
  18. Medically documented allergy towards the adhesive (glue) of plasters or unable to tolerate tape adhesive in the area of sensor placement
  19. Serious skin diseases (e.g. psoriasis vulgaris, bacterial skin diseases) located at places of the body, which potentially are possible to be used for localisation of the glucose sensor)
  20. Illicit drugs abuse
  21. Subject is currently abusing prescription drugs
  22. Alcohol abuse
  23. Use of pramlintide (Symlin), or other non-insulin glucose lowering agents including sulphonylureas, biguanides, DPP4-Inhibitors, , GLP-1 analogues, SGLT-1/ 2 inhibitors at time of screening
  24. Shift work with working hours between 10pm and 8am
  25. Sickle cell disease, haemoglobinopathy, or has received red blood cell transfusion or erythropoietin within 3 months prior to time of screening
  26. Eating disorder such as anorexia or bulimia
  27. Employed by Medtronic Diabetes or with immediate family members employed by Medtronic Diabetes
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02925299

Contacts
Contact: Roman Hovorka, PhD +44 1223 762 862 rh347@cam.ac.uk
Contact: Judy Sibayan, MPH, CCRP 813-975-8690 jsibayan@jaeb.org

Locations
United States, California
Stanford University Not yet recruiting
Palo Alto, California, United States, 95032
Contact: Bruce Buckingham, MD    650-725-6549    buckingham@stanford.edu   
Contact: Liana Hsu, RN    650-735-3939    ljhsu@stanford.edu   
United States, Colorado
University of Colorado Denver School of Medicine Barbara Davis Center Not yet recruiting
Aurora, Colorado, United States, 80045
Contact: Paul Wadwa, MD    303-724-6742    Laurel.Messer@ucdenver.edu   
Contact: Laurel Messer, RN, MPH, CDE    (303) 724-6742    Laurel.Messer@ucdenver.edu   
United States, Connecticut
Yale University Not yet recruiting
Hartford, Connecticut, United States, 06520
Contact: Stuart Weinzimer    203-785-7924    stuart.weinzimer@yale.edu   
Contact: Lori Carria    203-737-3595    lori.carria@yale.edu   
United States, Minnesota
International Diabetes Center at Park Nicollet Not yet recruiting
Minneapolis, Minnesota, United States, 55146
Contact: Amy Criego    952-993-1913    Mary.L.Johnson@ParkNicollet.com   
Contact: Mary L. Johnson, RN    952-993-1913    Mary.L.Johnson@ParkNicollet.com   
United Kingdom
University of Cambridge Not yet recruiting
Cambridge, Cambridgeshire County, United Kingdom, CB2 0QQ
Contact: Carlo Acerini, MD    +44 (0)1223 336 865    mt641@medschl.cam.ac.uk   
Contact: Martin Tauschmann, MD    +44 (0) 1223-769-080    mt641@medschl.cam.ac.uk   
Principal Investigator: Carlo Acerini, MD         
The Leeds Teaching Hospitals NHS Trust Not yet recruiting
Leeds, West Yorkshire, United Kingdom, LS9 7TF
Contact: Fiona Campbell, MD    44-1132-064-996    Jane.exall@nhs.net   
Contact: Jane Exall    44-1132-064-996    Jane.exall@nhs.net   
Sponsors and Collaborators
Jaeb Center for Health Research
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Cambridge University Hospitals NHS Foundation Trust
University of Colorado Denver School of Medicine Barbara Davis Center
International Diabetes Center at Park Nicollet
The Leeds Teaching Hospitals NHS Trust
Stanford University
Yale University
Investigators
Study Chair: Roman Hovorka, PhD University of Cambridge
Principal Investigator: Carlo Acerini, MD University of Cambridge
Principal Investigator: Fiona Campbell, MD The Leeds Teaching Hospitals NHS Trust
Principal Investigator: Bruce Buckingham, MD Stanford University
Principal Investigator: Stuart Weinzimer, MD Yale University
Principal Investigator: Amy Criego, MD International Diabetes Center at Park Nicollet
Principal Investigator: Paul Wadwa, MD University of Colorado Denver School of Medicine Barbara Davis Center
Principal Investigator: Korey Hood, PhD Stanford University
Principal Investigator: Dana Goldman, PhD University of Southern California
  More Information

Responsible Party: Jaeb Center for Health Research
ClinicalTrials.gov Identifier: NCT02925299     History of Changes
Other Study ID Numbers: DAN05
1UC4DK108520-01 ( US NIH Grant/Contract Award Number )
Study First Received: October 4, 2016
Last Updated: March 1, 2017
Individual Participant Data  
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes

Additional relevant MeSH terms:
Diabetes Mellitus
Autoimmune Diseases
Metabolic Diseases
Diabetes Mellitus, Type 1
Endocrine System Diseases
Glucose Metabolism Disorders
Immune System Diseases
Insulin, Globin Zinc
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 24, 2017